Dr. John Blass at Cornell has shown that the activity of three thiamine-dependent enzymes--transketolase, alphaketoglutarate dehydrogenase, and pyruvate dehydrogenase--are decreased in two dementias, Wernicke-Korsakoff Syndrome and Alzheimer's disease. In general, this decrease occurs in body tissues not directly affected by the disease process; this suggests that inactivation of these enzymes is not simply an effect of the underlying pathology but may be intimately related to the cause of each disease, perhaps directly or perhaps as a predisposing factor. The goal of this project is to clone the genes for these enzymes, beginning with transketolase by screening cDNA expression libraries from human brain and liver with antibodies made by the Blass group and with synthetic oligonucleotides whose sequence will be derived from microsequencing of purified protein provided by the Blass group. The cloned DNAs for these genes will then be used as probes to analyzed the structure and function of the genes in Alzheimer and Wernicke patients versus normal controls. We have also completed a small pilot experiment to analyzes Alzheimer brain for reverse transcriptase, in order to ask if a retrovirus might play a role in this disease.